痰液嗜酸性粒细胞与哮喘患者运动诱发支气管收缩对皮质类固醇的反应
Sputum eosinophils and the response of exercise-induced bronchoconstriction to corticosteroid in asthma.
作者信息
Duong MyLinh, Subbarao Padmaja, Adelroth Ellinor, Obminski George, Strinich Tara, Inman Mark, Pedersen Soren, O'Byrne Paul M
机构信息
Department of Medicine, McMaster University, 1200 Main St West, Room 3U-24, Hamilton, ON, Canada L8N 3Z5.
出版信息
Chest. 2008 Feb;133(2):404-11. doi: 10.1378/chest.07-2048. Epub 2007 Dec 10.
BACKGROUND
The relationship between eosinophilic airway inflammation and exercise-induced bronchoconstriction (EIB), and the response to inhaled corticosteroid (ICS) therapy was examined.
METHODS
Twenty-six steroid-naïve asthmatic patients with EIB were randomized to two parallel, double-blind, crossover study arms (13 subjects in each arm). Each arm compared two dose levels of inhaled ciclesonide that were administered for 3 weeks with a washout period of 3 to 8 weeks, as follows: (1) 40 vs 160 microg daily; and (2) 80 vs 320 microg daily. Baseline and weekly assessments with exercise challenge and sputum analysis were performed.
RESULTS
Data were pooled and demonstrated that 10 subjects had baseline sputum eosinophilia >or= 5%. Only high-dose ICS therapy (ie, 160 and 320 microg) significantly attenuated the sputum eosinophil percentage. Sputum eosinophil percentage significantly correlated with EIB severity, and predicted the magnitude and temporal response of EIB to high-dose therapy, but not to low-dose therapy (ie, 40 and 80 microg). Low-dose ICS therapy provided a significant reduction in EIB at 1 week, with little additional improvement thereafter, irrespective of baseline sputum eosinophil counts. In contrast, high-dose ICS therapy provided a significantly greater improvement in EIB in subjects with sputum eosinophilia compared to those with an eosinophil count of < 5%. The difference between the eosinophilic groups in the magnitude of improvement in EIB was evident after the first week of high-dose ICS therapy and increased with time.
CONCLUSIONS
These results suggest that eosinophilic airway inflammation may be important in modifying the severity of EIB and the response to ICS therapy. Measurements of sputum eosinophil percentage may, therefore, be useful in predicting the magnitude and temporal response of EIB to different dose levels of ICSs.
TRIAL REGISTRATION
clinicaltrial.gov; Identifier: NCT00525772.
背景
研究了嗜酸性气道炎症与运动诱发性支气管收缩（EIB）之间的关系以及对吸入性糖皮质激素（ICS）治疗的反应。
方法
26例未使用过类固醇的EIB哮喘患者被随机分为两个平行、双盲、交叉研究组（每组13名受试者）。每组比较两种剂量水平的吸入性环索奈德，给药3周，洗脱期为3至8周，如下：（1）每日40微克与160微克；（2）每日80微克与320微克。进行运动激发试验和痰液分析的基线及每周评估。
结果
汇总数据表明，10名受试者的基线痰液嗜酸性粒细胞增多≥5%。只有高剂量ICS治疗（即160微克和320微克）能显著降低痰液嗜酸性粒细胞百分比。痰液嗜酸性粒细胞百分比与EIB严重程度显著相关，并可预测EIB对高剂量治疗的反应程度和时间反应，但不能预测对低剂量治疗（即40微克和80微克）的反应。低剂量ICS治疗在第1周时能显著减轻EIB，此后几乎没有额外改善，无论基线痰液嗜酸性粒细胞计数如何。相比之下，与痰液嗜酸性粒细胞计数<5%的受试者相比，高剂量ICS治疗在痰液嗜酸性粒细胞增多的受试者中对EIB的改善明显更大。高剂量ICS治疗第1周后，嗜酸性粒细胞组在EIB改善程度上的差异明显，并随时间增加。
结论
这些结果表明，嗜酸性气道炎症可能对改变EIB的严重程度和对ICS治疗的反应很重要。因此，痰液嗜酸性粒细胞百分比的测量可能有助于预测EIB对不同剂量水平ICS的反应程度和时间反应。
试验注册
clinicaltrial.gov；标识符：NCT00525772。
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